Inorganic nitrite has recently been recognized to possess vascular activity that is enhanced in hypoxia. This has been demonstrated in humans in the forearm vascular bed. In animal models nitrite reduces pulmonary vascular resistance, but its effects upon the pulmonary circulation of humans have not yet been demonstrated. This paradigm is of particular interest mechanistically since the pulmonary vasculature is known to behave differently to the systemic. To investigate, 18 healthy volunteers were studied in a hypoxic chamber (inspired oxygen, 12%) or while breathing room air. Each received an infusion of sodium nitrite (1 micromol/min) or 0.9% saline. Three protocols were performed: nitrite/hypoxia (n = 12), saline/hypoxia (n = 6), and nitrite/normoxia (n = 6). Venous blood was sampled for plasma nitrite, forearm blood flow was measured by strain-gauge plethysmography, and pulmonary arterial pressure was measured by transthoracic echocardiography. Plasma nitrite doubled and clearance kinetics were similar whether nitrite was infused in hypoxia or normoxia. During hypoxia, nitrite increased forearm blood flow (+36%, P < 0.001) and reduced three separate indirect indexes of pulmonary arterial pressure by 16%, 12%, and 17% (P < 0.01). Pulmonary, but not systemic, arterial effects persisted 1 h after stopping the infusion, at a time when plasma nitrite had returned to baseline. No effects were observed during normoxia. Therefore, in hypoxic but not normoxic subjects, sodium nitrite causes arterial and pulmonary vasodilatation. In addition, hypoxia-induced pulmonary vasoconstriction was attenuated for a prolonged period and not dependent on a simultaneous elevation of plasma nitrite. This finding is consistent with the direct extravascular metabolism of nitrite to nitric oxide to effect hypoxia-associated bioactivity.
Traditionally, leg cycle ergometry is used to assess the power output of the lower limbs. However, it is suspected that the upper body makes a significant, albeit as yet unknown, contribution to the measured power output, and as such, the lean mass of the whole body should be considered during ergometric assessment. To test this idea, indices of mechanical power output were obtained from 11 subjects during high intensity leg cycle ergometry tests (20 second duration; 75 grams per kilogram total body mass) using two protocols: one with a standard handle-bar grip (with grip) and one with supinated wrists (without-grip). Peak mechanical power, mean mechanical power, fatigue index and total mechanical work values were calculated for each subject during each test and the sample mean differences associated with the two protocols were compared using paired Student t-tests. The with-grip protocol yielded significantly greater peak mechanical power output than the without-grip protocol (886+/-124 W and 815+/-151 W, respectively), suggesting a significant upper body contribution to the maximum power output measured for the legs. As a first step towards quantifying the upper body involvement during leg cycle ergometry, surface electromyography of the forearm musculature was measured in a twelfth subject whilst performing each of the test protocols. During the with-grip ergometer tests, the intensity of electrical activity in the forearm musculature was similar, if not greater than, the intensity of electrical activity recorded for the forearm musculature during 100% maximum voluntary hand grip-dynamometer contractions, suggesting maximum isometric-type forearm muscle contraction during the with-grip leg ergometry tests. These findings suggest that the performance of traditional-style leg cycle ergometry requires a muscular contribution from the whole body. As such, researchers should be mindful of this, both in terms of the allocation of ergometer loads, and in the analysis of blood-borne metabolites.
SUMMARYBackground: Uncertainty exists as to whether dysplastic polyps in ulcerative colitis should always be managed as dysplasia-associated lesions/masses requiring colectomy, or whether some can be managed by polypectomy. The prevalence of non-inflammatory polyps in ulcerative colitis is unknown. Aim: To compare dysplastic polyp occurrence in patients with ulcerative colitis and in patients without inflammatory bowel disease. Methods: The clinical, endoscopic and histological records of 150 ulcerative colitis patients (median disease duration, 10 years; 57% with pancolitis) undergoing colonoscopy were scrutinized for any polyp history. Two hundred and five patients undergoing colonoscopy for altered bowel habit, but without features suggestive of polyp presence, were used as a control group.
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